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Berlin Brandenburg

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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 28 July 2015, Vol.112(30), pp.9322-7
    Description: A cellular feature of Parkinson's disease is cytosolic accumulation and amyloid formation of α-synuclein (α-syn), implicating a misregulation or impairment of protein degradation pathways involving the proteasome and lysosome. Within lysosomes, cathepsin D (CtsD), an aspartyl protease, is suggested to be the main protease for α-syn clearance; however, the protease alone only generates amyloidogenic C terminal-truncated species (e.g., 1-94, 5-94), implying that other proteases and/or environmental factors are needed to facilitate degradation and to avoid α-syn aggregation in vivo. Using liquid chromatography-mass spectrometry, to our knowledge, we report the first peptide cleavage map of the lysosomal degradation process of α-syn. Studies of purified mouse brain and liver lysosomal extracts and individual human cathepsins demonstrate a direct involvement of cysteine cathepsin B (CtsB) and L (CtsL). Both CtsB and CtsL cleave α-syn within its amyloid region and circumvent fibril formation. For CtsD, only in the presence of anionic phospholipids can this protease cleave throughout the α-syn sequence, suggesting that phospholipids are crucial for its activity. Taken together, an interplay exists between α-syn conformation and cathepsin activity with CtsL as the most efficient under the conditions examined. Notably, we discovered that CtsL efficiently degrades α-syn amyloid fibrils, which by definition are resistant to broad spectrum proteases. This work implicates CtsB and CtsL as essential in α-syn lysosomal degradation, establishing groundwork to explore mechanisms to enhance their cellular activity and levels as a potential strategy for clearance of α-syn.
    Keywords: Parkinson’s Disease ; Amyloid ; Lysosomes ; Mass Spectrometry ; Protein–Lipid Interactions ; Cathepsin B -- Metabolism ; Cathepsin L -- Metabolism ; Cysteine -- Chemistry ; Lysosomes -- Metabolism ; Parkinson Disease -- Metabolism ; Alpha-Synuclein -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    In: Social Forces, 2013, Vol. 91(3), pp.747-784
    Description: The increase in high-skilled immigrants to the United States coincided with the expansion of the high-technology sector, and now a large share of Asian immigrants concentrate in high-tech industries. Despite much research on the relationship between ethnic concentration and labor market outcomes, the association between ethnic niche employment and earnings within the high-technology sector of the labor market has yet to be examined. This study compares the relationship between employment in ethnic niches and earnings within high- and low-tech industries among Asian immigrants. In low-technology industries, ethnic niches are generally associated with lower earnings compared with non-niches, but in high-technology industries, employment in an ethnic niche is associated with higher earnings. These patterns vary by gender and ethnic group. This association is partly explained by the industries that comprise ethnic niches, as non-Hispanic white immigrants also experience some of the same advantages and disadvantages.
    Keywords: Foreigners ; Comparative Analysis ; Labour Market ; Employment ; Ethnicity ; Gender ; High Tech Industries;
    ISSN: 0037-7732
    E-ISSN: 1534-7605
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  • 3
    Language: English
    In: Journal of the American Chemical Society, 30 October 2013, Vol.135(43), pp.15970-3
    Description: α-Synuclein (α-Syn), an intrinsically disordered protein, is associated with Parkinson's disease. Though molecular pathogenic mechanisms are ill-defined, mounting evidence connects its amyloid forming and membrane binding propensities to disease etiology. Contrary to recent data suggesting that membrane remodeling by α-syn involves anionic phospholipids and helical structure, we discovered that the protein deforms vesicles with no net surface charge (phosphatidylcholine, PC) into tubules (average diameter ∼20 nm). No discernible secondary structural changes were detected by circular dichroism spectroscopy upon the addition of vesicles. Notably, membrane remodeling inhibits α-syn amyloid formation affecting both lag and growth phases. Using five single tryptophan variants and time-resolved fluorescence anisotropy measurements, we determined that α-syn influences bilayer structure with surprisingly weak interaction and no site specificity (partition constant, Kp ∼ 300 M(-1)). Vesicle deformation by α-syn under a variety of different lipid/protein conditions is characterized via transmission electron microscopy. As cellular membranes are enriched in PC lipids, these results support possible biological consequences for α-syn induced membrane remodeling related to both function and pathogenesis.
    Keywords: Membranes, Artificial ; Amyloid -- Chemistry ; Alpha-Synuclein -- Chemistry
    ISSN: 00027863
    E-ISSN: 1520-5126
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 10 June 2014, Vol.111(23), pp.8321-8322
    Keywords: Behavioral sciences -- Anthropology -- Ethnology ; Social sciences -- Population studies -- Human populations ; Behavioral sciences -- Sociology -- Human societies ; Behavioral sciences -- Anthropology -- Ethnology ; Education -- Formal education -- Academic education ; Education -- Formal education -- Academic education ; Education -- Education politics -- Supply of education ; Behavioral sciences -- Anthropology -- Ethnology ; Behavioral sciences -- Anthropology -- Applied anthropology ; Behavioral sciences -- Sociology -- Human societies
    ISSN: 00278424
    Source: Archival Journals (JSTOR)
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  • 5
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 29 September 2015, Vol.112(39), pp.11993-4
    Description: Author contributions: D.M.K., P.R., and J.S.L. wrote the paper.
    Keywords: Activating Transcription Factor 3 -- Metabolism ; Ganglia -- Virology ; Herpesvirus 1, Human -- Physiology ; Virus Latency -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 6
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 23 August 2011, Vol.108(34), pp.14157-62
    Description: Class IA PI3Ks are activated by growth factor receptors and generate lipid second messengers that mediate downstream responses including cell growth, cell migration, and cell survival. The p85 regulatory subunit of PI3K contains Src homology-2 (SH2) domains that mediate binding to tyrosine-phosphorylated receptors or adaptor proteins to facilitate localization and activation of PI3K at the plasma membrane. We report here that persistent activation of PKC family members by phorbol ester stimulation in cells leads to phosphorylation of two serine residues at analogous sites on both SH2 domains of p85α (S361 and S652). The modified serine residues are located in the phospho-tyrosine binding pockets of the two SH2 domains, and in the crystal structures the phosphate moieties are predicted to occupy the same space as the phosphate moieties of bound phospho-tyrosine peptides. Consistent with this prediction, phosphorylation at these serine residues or mutation to aspartate inhibits binding of p85α to tyrosine-phosphorylated peptides. We provide evidence that protein kinase D, which is phosphorylated and activated by PKCs, mediates phosphorylation of S652 in the C-terminal SH2 domain. These results reveal cross talk between PKC signaling and PI3K signaling that impairs PI3K pathway activation under conditions of persistent PKC (and protein kinase D) activity.
    Keywords: Src Homology Domains ; Class Ia Phosphatidylinositol 3-Kinase -- Chemistry ; Enzyme Activators -- Metabolism ; Phosphoserine -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 7
    Language: English
    In: The Annals of the American Academy of Political and Social Science, 2015, Vol.662, pp.79-93
    Keywords: Intermarriage – Demographic Aspects ; Asian Americans – Social Aspects
    ISSN: 0002-7162
    Source: Cengage Learning, Inc.
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  • 8
    Language: English
    In: Annals, Vol.662 pp.79-246, 2015
    Keywords: Socioeconomic; Unassimilable; Intermarriage; Marriageable; Nationality; Immigration; Undesirable; Researchers; Recognition; Populations; Business & Corporate Law; Criminal Law & Procedure; Family Law; Governments; Immigration Law
    ISSN: 0002-7162
    E-ISSN: 1552-3349
    Source: Academic Law Reviews (LexisNexis®)
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  • 9
    In: Social Forces, 2013, Vol.91(3), pp.747-784
    Description: The increase in high-skilled immigrants to the United States coincided with the expansion of the high-technology sector, and now a large share of Asian immigrants concentrate in high-tech industries. Despite much research on the relationship between ethnic concentration and labor market outcomes, the association between ethnic niche employment and earnings within the high-technology sector of the labor market has yet to be examined. This study compares the relationship between employment in ethnic niches and earnings within high- and low-tech industries among Asian immigrants. In low-technology industries, ethnic niches are generally associated with lower earnings compared with non-niches, but in high-technology industries, employment in an ethnic niche is associated with higher earnings. These patterns vary by gender and ethnic group. This association is partly explained by the industries that comprise ethnic niches, as non-Hispanic white immigrants also experience some of the same advantages and disadvantages.
    Keywords: High Technology Industries -- United States -- Employees ; Minorities -- Employment -- United States
    ISSN: 0037-7732
    E-ISSN: 1534-7605
    Source: Project MUSE
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  • 10
    Language: English
    In: Focus on Autism and Other Developmental Disabilities, September 2019, Vol.34(3), pp.141-152
    Description: Deficits in social communication and interaction have been identified as distinguishing impairments for individuals with an autism spectrum disorder (ASD). As a pivotal skill, the successful development of social communication and interaction in individuals with ASD is a lifelong objective. Point-of-view video modeling (VM) has the potential to address these deficits. By presenting only what a person might see from his or her viewpoint, it may be more effective than other forms of VM, in limiting irrelevant stimuli and providing a clear frame of reference to facilitate imitation. The current study investigated the use of point-of-view VM in teaching social initiations (e.g., greetings). Using a multiple baseline across participants design, five kindergarten participants were taught greetings using a packaged intervention, which included point-of-view VM, video priming, verbal praise, reinforcement, and prompting. Immediately before and after viewing the entire point-of-view video model, the participants were evaluated on their greetings with a trained, typically developing peer serving as a communication partner. Specifically, the greetings involved participants’ abilities to shift their attention toward the peer who entered the room, maintain attention toward the peer, and engage in an appropriate greeting (e.g., hi, hello). Both generalization and maintenance were tested. Overall, the data suggest point-of-view VM is a promising intervention for increasing greetings. However, both generalization and maintenance were limited. Despite the limitations of the study and variable results, there are a number of implications moving forward for both practitioners and future researchers examining point-of-view modeling.
    Keywords: Autism Spectrum Disorder ; Point-of-View Video Modeling ; First-Person Perspective Video Modeling ; Social Initiations ; Greetings ; Social Communication and Interaction ; Medicine ; Education
    ISSN: 1088-3576
    E-ISSN: 1538-4829
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